Renal Replacement Therapy (RRT) is a class of medical treatments that artificially provides functions that would naturally be provided by the kidneys. RRT performs two primary functions: (i) ultrafiltration (removal of water from blood plasma), and (ii) solute clearance (removal of different molecular weight substances from blood plasma). Mechanical RRT generally involves an extracorporeal blood circuit that treats blood that is temporarily removed from and then returned to a patient. Devices used for RRT generally include: an extracorporeal blood circuit that extends from the patient through a filter and back to the patient; a pump acting on the blood circuit tube that moves the blood through the tube and filter; a filter where the blood components are separated and where the solute exchange takes place; and blood access devices. In addition, a mechanical RRT device may include a controller to regulate the pump(s), which in turn control the flow rate of blood and other fluids through the circuit, and detect blockages and leaks in the blood circuit.
In operation, blood from a patient flows through the RRT blood circuit at a flow rate determined by the blood pump speed. As the blood flows through the filter, certain fluids, solutes or both from the blood pass through the filter membrane and are extracted from the blood plasma. The extracted fluids with solutes flow from the filter through a filtrate tube and are temporarily stored in a filtrate bag. The extraction of fluids and/or solutes by the RRT device replaces or supplements the natural functions of the kidneys. Fluids may be injected into the remaining blood plasma which then flows through the blood circuit tube and is infused into the patient.
The filter in an RRT device, also called hemofilter or “dialyzer”, can be set up to perform fluid removal, solute clearance, or both. The RRT device may also operate with or without fluid replacement. “Clearance” and “ultrafiltration” are common terms used in RRT. “Clearance” is the term used to describe the net removal of substances, both normal and waste product, from the blood. “Ultrafiltration” is the term used to describe the removal from the blood plasma of plasma water, without significant affect on the concentration of small solutes in the blood plasma. In mechanical terms “Ultrafiltration” is the convective transfer of fluid out of the plasma compartment of a filter through pores in the filter membrane and into a filtrate output compartment of the filter.
Blood filters generally have a blood compartment within input and output ports connected to the blood circuit, a filter membrane, and a filtrate compartment. The membrane separates the blood compartment and the filtrate compartment in the filter. In a filter used primarily for ultrafiltration, the pores of the filter membrane may be hollow fibers having blood passages of approximately 0.2 mm or less in diameter. The filter membrane pass fluids, electrolytes and small and middle sized molecules (typically up to 50,000 Daltons) from the blood plasma. The ultrafiltrate output from the filtration pores is similar to plasma, but without the plasma proteins or blood cells. In an ultrafiltration filter, the concentration of small solutes is the same in the ultrafiltrate as in the plasma, and no clearance or concentration change is obtained of small solutes in the blood plasma that is returned to the patient. However, the ultrafiltration does remove water from the blood and is useful for treating patients suffering from fluid overload. During the ultrafiltration treatment of a fluid overloaded patient the fluid that is mechanically “filtered” or removed from blood is typically immediately replaced by the access fluid that has been stored in the body. As a result the excess fluid or “edema” in the legs, the abdomen and the lungs of the patient is reduced and the patient's condition is relieved.
Dialysis is a different form of RRT. Dialysis is the transfer of small solutes out of a blood plasma compartment of a filter by diffusion across the filter membrane. Dialysis occurs as a result of a concentration gradient across the filter membrane. Diffusion of small solutes occurs from the filter compartment with a higher concentration (typically the blood compartment) to a compartment with lower concentration (typically the dialysate compartment). Since the concentration of solutes in the plasma decreases, clearance is obtained. Fluid removal does not necessarily occur during dialysis.
Ultrafiltration can be combined with dialysis to remove both fluid and small solutes from the blood plasma during RRT. Hemofiltration is the combination of ultrafiltration and fluid replacement. The volume of the replacement fluid is typically much larger than is needed just for fluid control. The replacement fluid generally contains electrolytes, but not other small molecules. There is some clearance because there is a net removal of small solutes due to both replacing fluids without small solutes and ultrafiltration of fluid with small solutes. A primary difference between the ultrafiltration and hemofiltration treatments is that during the former the plasma water removed from blood is replaced by the natural excess fluid internally stored in the patient's body. During the later the replacement solution is supplied by the treatment in a form of an artificial infusion.
Generally, all modes of Renal Replacement Therapy involve the removal of blood (typically venous) from a patient and passing the blood through a hollow fiber filter where there occurs fluid removal and, if desired, a solute removal or exchange. After passing through the filter, the blood is returned to the blood stream of the patient. So-called “batch” type RRT devices extract and return blood through the same single lumen IV catheter or “needle” and blood tube by reversing the direction of the blood pump. More common “continuous” type devices extract and return blood continuously using one double lumen catheter in the same vein or separate catheters in two separate veins. Catheter and needles used in RRT are generally known as “blood access”. Some RRT patients have permanently lost their kidney function and need to undergo dialysis several times a week. These patients typically have surgically implanted or modified sites for blood access such as arterial-venous shunts or fistulas.
Congestive Heart Failure (CHF) patients can benefit from fluid removal by ultrafiltration of blood. CHF patients have functional kidneys, but suffer from fluid overload due to CHF. The kidneys of CHF patients are generally healthy but are not fully functioning due to the failing heart and low blood pressure. Because the kidneys are not fully functioning, fluids build up in the patient and the fluid overload contributes to the stress on the already failing heart. The kidneys do produce urine that is usually sufficient for the kidneys to remove toxic solutes.
CHF patients need an RRT treatment that removes excess fluid from the body. These patients typically do not require solute removal or a long-term chronic treatment as in the chronic dialysis patient. The fluid can be removed from the patient relatively quickly and the treatment stopped. The reduction of fluid overload should relieve the stress on the heart sufficiently so that the heart is able to resume adequate perfusion of the kidney. Even if the heart is unable to adequately perfuse the kidney after the fluid overload treatment, the patient often enjoys several days or weeks before the fluid overload condition again becomes sufficiently severe to undergo another ultrafiltration treatment. These CHF patients need a RRT treatment that is simple to establish and safe.
Fluid overload can lead to several painful and dangerous conditions, including excessive fluids in the lungs. If excessive fluid in the lungs is not promptly removed with a diuretic medication, CHF patients are often intubated and placed on a ventilator. If the initial diuretic therapy has little affect, more aggressive treatment with increasingly potent diuretics is needed. In addition, inotropic agents such as dobutamine are administered to increase the pumping function of the heart and raise the blood pressure. Higher blood pressure is expected to assist in the perfusion of the kidneys and make diuretics work. In more recent years, vasodilator therapy became a part of the standard therapy for a severely volume-overloaded, decompensated CHF patient. All the above-mentioned therapies as a rule require admission to an intensive care unit (ICU) of a hospital. Potentially dangerous side affects of drugs and the need for advanced monitoring and intubation are the main reasons for a typical ICU admission. ICU admissions are expensive and require specialized doctor and nurse caregivers.
Previously, standard drug therapy was frequently unable to remove excess fluid rapidly enough to prevent hospitalization. There is a clear and unmet clinical need for a CHF treatment that allows physicians to rapidly, controllably and safely remove a clinically significant amount of fluid from a CHF patient. Such a treatment would potentially reduce the need for excessive hospital admissions and decrease the duration of hospital stays.
Ultrafiltration (one mode of Renal Replacement Therapy) is useful for removal of excess fluid from a patient, especially in CHF patients whose kidneys are not working but are generally healthy. Ultrafiltration has not been used widely in the treatment of patients with CHF, despite its clinical benefits for treating fluid overload. There are several issues that have in the past limited the use of currently available ultrafiltration devices. One of these factors is that prior ultrafiltration devices draw large volumes of blood out of the body and, thus, require so called central venous access. Central venous access implies that a relatively large diameter catheter is placed with its tip in a major vein in the “center” of the patient's body. Typically the central catheter is placed in the superior vena cava or right atrium of the heart of the patient. This procedure requires specialized skill and is also associated with serious complications such as bleeding, perforated lung or heart and infections. As a result, mechanical fluid removal in CHF patients has in the past been performed in the ICU of a hospital where resources, training and adequate nursing monitoring are available.
With the increasing prevalence of decompensated CHF and the increased cost of hospital admission and even more so of an ICU treatment, a strong need has emerged for a new technology that will allow fluid removal in the non critical care setting. This need is for a device and technique that is simple and safe so that it could be used in the outpatient setting, doctor's offices, Emergency Rooms (ER) and general hospital floors. Such treatment would be acceptable if access to venous blood was established via a peripheral vein in the patient's arm or other peripheral vascular site on the patient. An advantage of accessing blood through a peripheral vein in the arm is well recognized. Unlike the central veins, the peripheral veins are close to skin and easier to identify. Physicians and nurses are trained to place needles and catheters in the peripheral veins of an arm. Venopunctures are easy to monitor for infiltration of fluid and thrombosis and the control of infection is simpler than with central catheters. Also, the potential loss of a peripheral vein to thrombosis is less critical.